Philip J. Kranzusch, Amy Si-Ying Lee, James M. Berger, Jennifer A. Doudna
Innate immune recognition of foreign nucleic acids induces protective interferon responses. Detection of cytosolic DNA triggers downstream immune signaling through activation of cyclic GMP–AMP synthase (cGAS). We report here the crystal structure of human cGAS, revealing an unanticipated zinc-ribbon DNA-binding domain appended to a core enzymatic nucleotidyl transferase scaffold. The catalytic core of cGAS is structurally homologous to the RNA sensing enzyme, 2′–5′ oligo-adenylate synthase (OAS), and …
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